Nanotechnologists see big things through the looking glass

By Scott LaFee

Churning and drifting through the world's oceans -- indeed in any place where there is water -- are diatoms: single-celled, planktonic algae that are easily overlooked and generally unremarked upon until you actually see one through a microscope.

Then, they become small wonders, possessors of a singular kind of crystalline beauty. Each diatom species -- worldwide estimates range from 100,000 to 1 million -- boasts its own distinct shape. Some resemble pill boxes, others look like barrels, pincushions, flowers, flagpoles, spoked wheels, splashing raindrops, ladders or stars.

And all are made of glass.

For centuries, diatomists (scientists who study diatoms) focused their microscopes primarily upon the task of finding and describing these variegated species. There was a certain thrill in that (and for a while, a kind of art that consisted of assembling diatoms into dramatic scenes), but lately something has been happening. Others are taking note of diatoms: engineers, chemists and materials scientists who admire them not only for their biological beauty, but also for the potential of their microscopic architecture.

"You show a picture of a diatom to scientists," said David Wright, a professor of chemistry at Vanderbilt University, "and you've immediately got your audience. The structure of these organisms is so amazing, so varied. There's nothing in modern science to match it."

Which got some people thinking small.

"The goal of nanotechnology is to synthesize incredibly tiny structures (on scales of millionths of a meter) that can be used for all sorts of things in medicine, research, engineering and industry," said Mark Hildebrand, a professor of biology and diatomist at the Scripps Institution of Oceanography. "But we're never going to be able to build structures like diatoms in a test tube, at least not anytime soon, so why not find ways to use or make diatoms that will do what we want them to do on the nano-scale?"

Why not indeed.

Nature's marbles

Current nanotechnologies are mightily constrained by cost, time and difficulty. To create three-dimensional objects with features smaller than the width of a hair requires adding layer upon layer of material until the final shape is achieved. More exotic nano-objects like tubes built of carbon molecules or cage-like fullerenes are even harder to build, and most remain largely in the province of scientific curiosities.

Yet the promise of nanotechnology is indisputably compelling. If researchers could design and build structures at the scale of single molecules or atoms, the world of possibilities would be metaphorically huge: drug factories the size of pinheads, computers in the brain to aid memory, robots moving through the bloodstream to repair internal injury or disease.

"It would change what it means to be human," said Richard Smalley, a Rice University chemist and Nobel laureate, in the journal Physics Today.

One look at diatoms and it's obvious that nature has already figured out how to build small and cheap. "In the lab, you can grow billions of diatoms in a week for just a few dollars," said Hildebrand.

But growing them is the easy part. Exploiting their nanotechnological potential will require that scientists intimately understand how diatoms become what they are. And that, at the moment, is a very big and largely unanswered question.

The basic biology is broadly known. Diatoms are found in every body of water on Earth, an abundance and ubiquity that is essential to life on this planet. Diatoms form the base of the food chain, the main meal of most zooplankton. They represent the primary source of energy in the ocean. Though comprising just one percent of the planet's biomass, diatoms generate about half of the Earth's photosynthesis -- the conversion of carbon dioxide, nutrients and light into consumable sugars -- and produce roughly a quarter of the planet's atmospheric oxygen.

But nanotech's interest in diatoms is strictly superficial. Every diatom is encased in an intricate shell -- or frustule -- made of silica, the stuff of glass. Diatoms make these frustules quickly, at room temperature and pressure, in ordinary water, without requiring or producing a single toxic chemical. No human manufacturing process can make a similar claim.

It is the astounding geometric shapes of these frustules and their elaborate pore patterns (through which the internal cell of the diatom pulls in nutrients) that attract nanotechnologists, who see them as ideal models for nano-scale gears, optics or various kinds of microfilters.

Some researchers are prospecting for naturally occurring diatoms that might fit a particular nano-need, but others contend that the long-term route to success is learning how to induce nature to do the job for them.

"Ultimately, we'd like to be able to genetically manipulate them, to alter the genes responsible for structure so that the diatom will build what we want at the size we want," said Hildebrand, one of the leading researchers pushing this approach.

"For example," said Thomas Manning, a professor of chemistry at Valdosta State University in Georgia, "the element gadolinium (Gd) is used in MRIs. But since it is toxic by itself, gadolinium needs to be trapped by a chemical cage before it is injected into the body. It might be possible to genetically engineer a diatom to produce a nanocrystal composed of Gd salt that is insoluble in the body. You could cream up a thousand applications like this, from particles used in paper coatings to electronic components to medical applications."

Self-assembled

How diatoms build themselves at all remains incompletely explained. There are two basic shapes -- pennate (elongated) or centric (round) -- but boundless variations that incorporate spines, wings and other exotic-looking protuberances.

"We're not sure what purpose these serve," said Hildebrand. "They may help keep the diatom at a certain depth in the water. Silica sinks, and diatoms need to be close to sunlight for photosynthesis. Or maybe the spines and such act as a defense against predatory zooplankton."

Diatoms generally reproduce asexually through cell division: a mother cell splitting into two daughter cells. To create their glassy frustules, diatoms extract from surrounding seawater a dissolved form of silica called silicic acid, importing it into a membrane-bound compartment called the silica deposition vesicle (SDV), where the silicic acid is shaped into a hard shell.

The particulars of that process are a matter of much scientific investigation. In 1999, chemist Nils Kroger at the University of Regensburg in Germany isolated a protein involved in directing the process. Other proteins have since been found. Hildebrand, for example, has identified proteins responsible for pulling silicic acid into the cell.

Parsing out such details is critical to being able to eventually manipulate the whole shaping process. Similarly, researchers need to map the entire genomes of targeted species so that they will know what to look for. The first such genetic sequencing occurred earlier this year when Hildebrand and colleagues published the genome for a diatom called Thalassiosira pseudonana.

"We're at the beginning of a long road," Hildebrand said. "We need to be able to differentiate these genes, find the ones held in common and the ones that make each species unique."

That's not the least of the challenges. Silica is a material much appreciated in science and industry. It's inert. It doesn't react with most substances or easily biodegrade. It's why test tubes are made of glass.

But many potential applications demand something else, said Ken Sandhage, a professor of materials science and engineering at the Georgia Institute of Technology.

"You may want a structure that is highly biodegradable for drugs, or one that is a good conductor or magnetic."

Sandhage has taken the first steps toward doing that. In a paper published in 2002, he described baking diatom frustules at 1,652 degrees Fahrenheit for four hours in the presence of magnesium gas. The result: The diatom's silica atoms were completely displaced, creating a perfect replica of the frustule composed entirely of ceramic magnesium oxide.

Richard Gordon, a diatomist at the University of Manitoba, admiringly called the conversion a "Star Trek replicator."

Sandhage has since repeated the feat, producing frustules composed of titanium oxide -- a widely used and useful compound -- and predicts the same can be done with other materials.

Still Sandhage (like other scientists) cautions against expecting science fictionesque breakthroughs anytime soon. "People have only been seriously at this for five years, and there's a lot remaining to be figured out. But I don't see any major impediments or barriers to doing great things. We've discovered a new tool. Now we're trying to figure out what we can do with it."